1. Field of the Invention
The invention provides a method and composition for treating inflammatory disease and more particularly a composition and method for treating inflammatory disease of the nose, paranasal sinuses and ears.
2. Prior Art
Inflammatory disease of the paranasal sinuses is a common disorder afflicting many people. It is characterized by repeated episodes of inflammation, precipitated initially by environmental factors such as smoke, pollutants or allergens, and often followed by a secondary bacterial infection. Exposure to such environmental inhalants stimulates the first stage of an edematous swelling of the membranes of the nose and a partial blockage of sinus drainage. The stroma becomes hyperemic, edematous and infiltrated with neutrophils, lymphocytes, and plasma cells. Serous and mucinous fluid exudes though the epithelium. Clinically these changes manifest as nasal stuffiness and rhinorrhea. If bacterial infection is superimposed, neutrophils dominate the inflammatory infiltrates that become evident as a thick purulent discharge.
Similar reactions to allergens and infectious agents occur in the mucosa of the paranasal sinuses and readily occlude the sinus ostia (openings). Superimposed bacterial infections of the occluded sinuses are referred to as sinusitis and can lead to serious complications depending on the location of the sinus. Ethmoidal air cell infection may spread into the orbital soft tissue and the meninges. Frontal sinusitis can result in meningitis and osteomyelitis of the frontal bone. Sphenoiditis may lead to retrobulbar neuritis and cavernous sinus thrombosis. The current treatment of this disorder involves a combination of the use of antibiotics, both systemic and topical anti-inflammatory agents and decongestants. More recently topical steroid sprays have been introduced as well as cromolyn which intervenes in this inflammatory process and produces clinical improvement in some of these patients. Unfortunately, many of these patients continue to have advancing disease that leads to total obstruction and a chronic sinusitis. These patients ultimately undergo surgical intervention. The classical surgical techniques involve radical exoneration of polypoid tissue from the nose and paranasal sinuses and the establishment of proper drainage. Such surgery is performed in the hospital under general anesthesia where a fair amount of bleeding is encountered along with some morbidity, not to mention the surgical risks of ocular and intracranial complications of such an extensive sinus surgery.
The presence of the inflammatory process in the nasal and paranasal mucosa often gives rise to polyp formation. Persistence of these inflammatory changes leads to infiltration by neutrophils, lymphocytes and eosinophiles. These inflammatory sequence of events have been well described in the medical literature and many cells have been implicated in this inflammatory process. It is well known from descriptive pathology that the inflammatory and hyperplastic phase is characterized by following stages:
I. edematous stage,
II. granular or infiltrating stage,
III. fibrous stage,
IV. mixture of any of these stages;
V. chronic inflammation with exudation.
The usual sequence of pathological events is that the submucous tissue is infiltrated with serum and leukocytes fill the voids within the mesh (stage I). The capillaries become dilated and the mucous membrane is greatly thickened and erythematous (stage II). The result of this edema is the engorgement of the subepithelial structures. In stage III the serum and leukocytes escape through the epithelial covering of the mucosa where they become mixed with bacteria and epithelial debris as well as mucous. These secretions, initially thin, later become thicker and more viscous. Some of the fibrin from the serum transudates. Stage IV is usually characterized by the resolution and the absorption of the exudate. Unfortunately stage five often results, in which the inflammatory process progresses from the congestive to the purulent type. During stage V, the leukocytes are being shed in immense numbers. At this stage the tissue changes become permanent with increasing fibrosis and a chronic condition is established. Because of the increasing blockage, phlebitis of the perforating veins and blockage of the drainage of the sinuses occurs.
Recent advances in surgical techniques have produced such tools as Hopkins lenses and endoscopic equipment suitable for the visualization of the osteo meatal complex of the sinuses. These instruments and techniques have reduced some of the complexity of the surgery and improved intranasal visualization during surgery. Unfortunately, the continued costs of management have remained high and surgical intervention and physical removal of polyps has not offered a cure for, or the resolution of the underlying disease. These polyps have the tendency to recur in spite of extensive and even radical sinus surgery.
There are numerous medical classifications of chronic inflammatory ear disease. The middle ear cleft is connected to the nasopharynx by means of an elongated ostium referred to as the Eustachian tube. The ear is subject to frequent inflammatory illnesses beginning in childhood. Serous otitis media of childhood is quite frequent as well as acute otitis media. These two conditions alone probably account for the majority of visits to the pediatric doctor's office and may constitute the key market for pediatric antibiotics. These early disorders frequently lead to more chronic conditions such as secretory-adhesive otitis media and chronic otitis media. These more advanced conditions often require surgical intervention in the form of draining the ears surgically and placing tubes in the tympanic membrane for longer term middle ear cleft drainage and ventilation. This procedure is one of the most commonly performed operations in the US. This represents significant monetary costs to society as well as occasional anesthesia morbidity given the frequency of the procedure. The clinical etiology of chronic otitis media is almost identical to that of chronic sinusitis where allergic, environmental, viral, and microbial factors have been implicated. Anatomically the middle ear, mastoid air cells, and the Eustachian tube complex and the ciliary mucosal lining bear remarkable relationship to other paranasal sinuses described above. The pathophysiology as well as the cellular immunology of chronic otitis media is similar to chronic sinusitis if not one of the same. It is the contention of the present inventors that the method of treating chronic inflammatory sinusitis described herein also applies to the treatment of chronic otitis media.